Two Part (Phase1b/ Phase3) Trial of Subcutaneous Dostarlimab Plus Carboplatin-Paclitaxel in Participants With Primary Advanced or Recurrent Endometrial Cancer

An Open-label, Multicenter, 2-Part Study: A Phase 1b Dose Selection Followed by a Randomized Phase 3 to Evaluate the Pharmacokinetics, Efficacy, and Safety of Subcutaneous Dostarlimab Plus Carboplatin-Paclitaxel Versus Intravenous Dostarlimab Plus Carboplatin-Paclitaxel in Participants With Primary Advanced or Recurrent Endometrial Cancer (SAPPHIRE)

Inclusion Criteria:

* Participant is at least 18 years of age (or the legal age of consent in the jurisdiction in which the trial is taking place) at the time of signing the Informed Consent Form (ICF).
* Participant has primary Stage III or Stage IV disease or first recurrent EC.
* Participant must have a documented Mismatch repair (MMR)/Microsatellite Instability (MSI) status.
* Participant is capable of giving signed informed consent, including compliance with the requirements and restrictions listed in the ICF and in the protocol.
* Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 for Part 1 and an ECOG performance status of 0 or 1 for Part 2.
* Participant has adequate organ function.

Exclusion Criteria:

* Participant has history of or active autoimmune disease that has required systemic treatments within the 2 years prior to screening.
* Participant has a history of severe allergic and/or anaphylactic reactions to chimeric, human or humanized antibodies, fusion proteins, or known hypersensitivity to carboplatin, paclitaxel or dostarlimab components or excipients.
* Participant has received prior therapy with anti-programmed death protein 1 (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti-PD-L2 agent.
* Participant has known uncontrolled brain or central nervous system (CNS) metastases.

Dostarlimab will be administered as SC injection and IV infusion

Carboplatin and paclitaxel will be administered as an IV infusion

Participants will receive SC dostarlimab in Cohorts 1, 2, 4, 5 and 6, at different doses, to determine the doses of SC dostarlimab that will yield drug exposures comparable to approved IV dosing regimens. Participants in Cohort 3 will receive IV dostarlimab. Participants in all cohorts will receive carboplatin and paclitaxel. After 6 cycles, all participants will receive IV dostarlimab for up to 3 years until progression, death, or intolerable toxicities.

Eligible participants will be randomly assigned to receive either SC dostarlimab or IV dostarlimab (standard of care arm) in a 1:1 ratio. Participants randomized to the experimental arm will receive SC dostarlimab in combination with carboplatin and paclitaxel for 6 cycles, followed by SC dostarlimab monotherapy for up to 3 years of treatment in total. Participants randomized to the standard of care arm will receive IV dostarlimab in combination with carboplatin and paclitaxel for 6 cycles, followed by IV dostarlimab monotherapy for up to 3 years of treatment in total.